We propose to determine whether immunoglobulin aggregates form in vivo in conditions associated with hypoalbuminemia and/or hypergamma-globulinemia, similar to what we have observed in vitro. This will be studied in an animal model of chronic hypoalbuminemia and the role of the mononuclear phagocyte system in clearing immunoglobulin aggregates will be determined. The effects of these aggregates on immune responses and tissue deposition will also be studied. Studies of human sera will crrelate the presence of immune complex-like reactivity with serum concentrations of immunoglobulin and albumin. Sera from three groups of patients in whom we believe circulating immunoglobulin aggregates, rather than antigen-antibody complexes, are present (paraproteinemias, metastatic malignancy, Laennec's cirrhosis) will be studied to determine whether the immune complex-like materials present have features characteristic of immunoglobulin aggregates rather than antigen-antibody complexes. Finally, the role of immunoglobulin aggregates on cell-mediated immune functions in these patients will be studied.